{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T20:37:34Z","timestamp":1791059854810,"version":"4.1.0"},"reference-count":212,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,10]],"date-time":"2022-09-10T00:00:00Z","timestamp":1662768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R00EY028223"],"award-info":[{"award-number":["R00EY028223"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY029680"],"award-info":[{"award-number":["R01EY029680"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY028884"],"award-info":[{"award-number":["R01EY028884"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Indiana University School of Medicine","award":["R00EY028223"],"award-info":[{"award-number":["R00EY028223"]}]},{"name":"Indiana University School of Medicine","award":["R01EY029680"],"award-info":[{"award-number":["R01EY029680"]}]},{"name":"Indiana University School of Medicine","award":["R01EY028884"],"award-info":[{"award-number":["R01EY028884"]}]},{"name":"Glaucoma Foundation","award":["R00EY028223"],"award-info":[{"award-number":["R00EY028223"]}]},{"name":"Glaucoma Foundation","award":["R01EY029680"],"award-info":[{"award-number":["R01EY029680"]}]},{"name":"Glaucoma Foundation","award":["R01EY028884"],"award-info":[{"award-number":["R01EY028884"]}]},{"name":"IUPUI Open Access Publishing Fund","award":["R00EY028223"],"award-info":[{"award-number":["R00EY028223"]}]},{"name":"IUPUI Open Access Publishing Fund","award":["R01EY029680"],"award-info":[{"award-number":["R01EY029680"]}]},{"name":"IUPUI Open Access Publishing Fund","award":["R01EY028884"],"award-info":[{"award-number":["R01EY028884"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Inherited retinal degeneration is a group of blinding disorders afflicting more than 1 in 4000 worldwide. These disorders frequently cause the death of photoreceptor cells or retinal ganglion cells. In a subset of these disorders, photoreceptor cell death is a secondary consequence of retinal pigment epithelial cell dysfunction or degeneration. This manuscript reviews current efforts in identifying targets and developing small molecule-based therapies for these devastating neuronal degenerations, for which no cures exist. Photoreceptors and retinal ganglion cells are metabolically demanding owing to their unique structures and functional properties. Modulations of metabolic pathways, which are disrupted in most inherited retinal degenerations, serve as promising therapeutic strategies. In monogenic disorders, great insights were previously obtained regarding targets associated with the defective pathways, including phototransduction, visual cycle, and mitophagy. In addition to these target-based drug discoveries, we will discuss how phenotypic screening can be harnessed to discover beneficial molecules without prior knowledge of their mechanisms of action. Because of major anatomical and biological differences, it has frequently been challenging to model human inherited retinal degeneration conditions using small animals such as rodents. Recent advances in stem cell-based techniques are opening new avenues to obtain pure populations of human retinal ganglion cells and retinal organoids with photoreceptor cells. We will discuss concurrent ideas of utilizing stem-cell-based disease models for drug discovery and preclinical development.<\/jats:p>","DOI":"10.3390\/biology11091338","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T20:52:25Z","timestamp":1663015945000},"page":"1338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Drug Discovery Strategies for Inherited Retinal Degenerations"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1449-7911","authenticated-orcid":false,"given":"Arupratan","family":"Das","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4696-4836","authenticated-orcid":false,"given":"Yoshikazu","family":"Imanishi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,10]]},"reference":[{"key":"ref_1","unstructured":"Rodieck, R.W., and Rodieck, R.W. 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